Table 1.
Candidate regulators of cognitive decline identified through genome-wide molecular profiling of human brain cells. Representative candidate genes associated with cognitive decline were identified through module-trait network, local regulatory network, or key driver analyses. For the genes presented in bold, the association with neuropathological traits (e.g., increased Aβ and/or pTau levels) was further validated by means of functional assays in cell cultures (see text for further details and references)
| Module-trait network analysis | Local regulatory network analysis | Key driver analysis |
|---|---|---|
| AK4 (adenylate kinase 4) | C1QTNF4 (C1q and TNF related 4) | CCT5 (chaperonin containing TCP1 subunit 5) |
| ANKRD40 (ankyrin repeat domain 40) | DHRS11 (dehydrogenase/reductase 11) | COMT (catechol-O-methyltransferase) |
| BCL2L1 (BCL2 like 1) | NPM3 (nucleophosmin/nucleoplasmin 3) | GNA12 (G protein subunit alpha 12) |
| FBXO2 (F-box protein 2) | NUPR1 (nuclear protein 1, transcriptional regulator) | HSPA2 (heat shock protein family A member 2) |
| HSPB2 (heat shock protein family B member 2) | RABEP2 (rabaptin, RAB GTPase binding effector protein 2) | PDHB (pyruvate dehydrogenase E1 beta subunit) |
| IGFBP5 (insulin line growth factor binding protein 5) | SCG3 (secretogranin III) | RGS4 (regulator of G protein signaling 4) |
| INPPL1 (inositol polyphosphate phosphatase like 1) | SEMA3F (semaphorin 3F) | ST18 (C2H2C-type zinc finger transcription factor) |
| ITPK1 (inositol-tetrakisphosphate 1-kinase) | SLC22A23 (solute carrier family 22 member 23) | |
| KIF5B (kinesin family member 5B) | STAU1 (staufen double-stranded RNA binding protein 1) | |
| PLXNB1 (plexin B1) | TRIOBP (TRIO and F-actin binding protein) | |
| SASH1 (SAM and SH3 domain containing 1) | ||
| SLC6A12 (solute carrier family 6 member 12) | ||
| VAT1 (vesicle amine transport 1) |